The overall objective of this contract is to identify and modify the structure of peptides to increase their potency and broaden their specificity with regard to the MHC restriction elements that can recognize them and present them to the human immune system. The result of these efforts should pave the way for testing the feasibility of peptide-based vaccines to prevent and/or treat important human infectious diseases. The specific diseases targeted with these studies are malaria caused by P. falciparum, human immunodeficiency virus (HIV) infection, and hepatitis B virus (HBV) infection. Specific aims: 1) To identify and modify human class I restricted apitopes such that a single peptide will be recognized and be immunogenic when presented by multiple HLA-A, B or C alleles; 2) To identify and modify human class II restricted apitopes such that a single peptide will be recognized and be immunogenic when presented by multiple HLA-DR alleles: 3) To combine the MHC class II epitopes defined under Specific Aim (2) with cytotoxic T lymphocytes (CTL) and B cell epitopes to produce highly immunogenic, broadly crossreactive CTL responses and antibody responses.